Magnetic resonance imaging (MRI) has become one of the most widely used imaging modalities in clinical practice that provides soft tissue images depicting both anatomy and pathologies. Since MRI signal arises from protons, water-poor structures, such as bone and tissue calcification, are essentially invisible.
Tissue calcification is an important biomarker for human disease, with microcalcifications being of paramount importance for the detection of breast cancer. However, MRI, now the standard of care for screening high-risk women for breast cancer, is unable to detect such calcifications.
About 80% of MRI protocols in North America employ injected contrast agents that improve tissue contrast and may give additional information {Caravan, 2006; Caravan, 1999}. The most commonly used MRI contrast agents are thermodynamic and kinetically stable low molecular weight gadolinium chelates that alter the relaxivity properties of the surrounding water {Bottrill, 2006}. While a wide range of nonspecific contrast agents are being used in clinical applications for evaluation of physiological parameters, the development of efficient targeted MRI contrast agents directed at specific molecular entities has dramatically expanded the range of possible applications for MRI by combining the noninvasiveness and high spatial resolution of MRI with the specific localization of molecular targets {Weinmann, 2003}. However, previous studies aimed at the development of bone-seeking agents, have shown that the Gd3+ complex of DOTP5− [1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonate)] failed to enhance the surrounding water signal when complexed to the bone {Alves, 2003}.